Monoclonal antibodies have great potential as a unique set of highly specific reagents for the prophylaxis, diagnosis and therapy of human diseases. However, a major problem encountered is the immunogenicity of these murine antibodies which limits their usefulness. In addition, human antibodies may be more efficient than mouse antibodies in mediating biological effector functions such as antibody-dependent cellular cytotoxicity in human patients. It would be a major advance to create a routine system for producing human monoclonal antibodies. The aim of our research is to generate a strain of transgenic mice that can rearrange human immunoglobulin genes, and thus, provide a functional human antibody repertoire. Mouse hybridomas could then be produced from such a mouse, using conventional techniques, that are producing human monoclonal antibodies.